ArticleCurrent biology : CB2021
EPHA2-dependent outcompetition of KRASG12D mutant cells by wild-type neighbors in the adult pancreas.
Article in Current biology : CB, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 54 citations in OpenAlex.
- A ternary association of KRas, EphA2, and integrins controls PDAC cell behavior.The Journal of biological chemistry · 2026Article
- Review
- Avidity-optimized TCR-T cells target KRAS neoantigens for potent cancer clearance and tumor microenvironment remodeling.Frontiers in immunology · 2026Article
- Ovarian tumor cells gain competitive advantage by actively reducing the cellular fitness of microenvironment cells.Nature biotechnology · 2025Article
- Cell Death, Compensatory Proliferation, and Cell Competition.Annual review of genetics · 2025Review
- Article
- Sustained NF-κB activation allows mutant alveolar stem cells to co-opt a regeneration program for tumor initiation.Cell stem cell · 2025Article
- TRIP13 protects pancreatic cancer cells against intrinsic and therapy-induced DNA replication stress.NAR cancer · 2025Article
- Visualizing cellular interactions: intravital imaging in tumor microenvironment.Frontiers in immunology · 2025Review
- The αvβ6 integrin specific virotherapy, Ad5British journal of cancer · 2024Article
- Tumor Promoters and Opportunities for Molecular Cancer Prevention.Cancer discovery · 2024Review
- Tumor initiation and early tumorigenesis: molecular mechanisms and interventional targets.Signal transduction and targeted therapy · 2024Review
- Beyond genetics: driving cancer with the tumour microenvironment behind the wheel.Nature reviews. Cancer · 2024Review
- Bat Motion can be Described by Leap Frogging.Bulletin of mathematical biology · 2024Article
- Cell competition and cancer from Drosophila to mammals.Oncogenesis · 2024Review
- The role and mechanism of compressive stress in tumor.Frontiers in oncology · 2024Review
- Epithelial recognition and elimination against aberrant cells.Seminars in immunopathology · 2024Review
- Article
- Pancreatic cancer epigenetics: adaptive metabolism reprograms starving primary tumors for widespread metastatic outgrowth.Cancer metastasis reviews · 2023Review
- Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
As we age, our tissues are repeatedly challenged by mutational insult, yet cancer occurrence is a relatively rare event. Cells carrying cancer-causing genetic mutations compete with normal neighbors for space and survival in tissues. However, the mechanisms underlying mutant-normal competition in adult tissues and the relevance of this process to cancer remain incompletely understood. Here, we investigate how the adult pancreas maintains tissue health in vivo following sporadic expression of oncogenic Kras (KrasG12D), the key driver mutation in human pancreatic cancer. We find that when present in tissues in low numbers, KrasG12D mutant cells are outcompeted and cleared from exocrine and endocrine compartments in vivo. Using quantitative 3D tissue imaging, we show that before being cleared, KrasG12D cells lose cell volume, pack into round clusters, and E-cadherin-based cell-cell adhesions decrease at boundaries with normal neighbors. We identify EphA2 receptor as an essential signal in the clearance of KrasG12D cells from exocrine and endocrine tissues in vivo. In the absence of functional EphA2, KrasG12D cells do not alter cell volume or shape, E-cadherin-based cell-cell adhesions increase and KrasG12D cells are retained in tissues. The retention of KRasG12D cells leads to the early appearance of premalignant pancreatic intraepithelial neoplasia (PanINs) in tissues. Our data show that adult pancreas tissues remodel to clear KrasG12D cells and maintain tissue health. This study provides evidence to support a conserved functional role of EphA2 in Ras-driven cell competition in epithelial tissues and suggests that EphA2 is a novel tumor suppressor in pancreatic cancer.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.